The primary objective of this project is to develop new approaches to the surgical management of cutaneous melanoma. In this regard, a major controversy exists over whether early lymph node dissection in patients with clinically negative (non-palpable lymph nodes offers any therapeutic advantage over observation and later dissection when the patient has developed clinically obvious nodal metastases. Since only 20% of such patients will have micrometastases found at the time of elective node dissection, 80% of such patients will be exposed to the morbidity and expense of an operative procedure from which they can derive no benefit. In this context, lymphatic mapping and sentinel lymphadenectomy (SLND) was proposed as a method to pathologically stage the regional lymph nodes without performing elective LND. Only patients with histologically proven sentinel node (NS) metastasis undergo complete LND. Thus, LND can be undertaken earlier for regional metastasis, and can be avoided completely in the absence of regional involvement thus sparing those with tumor free SN the morbidity of radical node dissection. This makes SLND a rational alternative to routine elective LND or nodal observation. Studies performed at institutions across the world have verified the validity of the SN concept and accuracy of SLND as a staging procedure. The specific aims of the proposal are to continue research on the development of these concepts and determine whether the techniques provide a survival benefit for melanoma. Aim 1- Conduct a multi-center trial which evaluate the application for intraoperative lymphatic mapping and selective lymphadenectomy for the management of clinical stage I melanoma. Aim 2- Improve the accuracy of sentinel node identification by improvements in surgical pathology technology. Aim 3- Develop more sensitive and accurate methods for identifying patients with systematic subclinical melanoma micrometastases, alone or combined with regional nodal metastases.